Wednesday, December 17, 2025 12/17/2025

The Role of Cellular Senescence in Carpal Tunnel Syndrome

Award Number: R01AR076347
ORGANIZATION: NATIONAL INSTITUTE OF ARTHRITIS & MUSCULOSKELETAL & SKIN DISEASES
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 09/10/2020
PERIOD OF PERFORMANCE END DATE: 11/30/2026

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The Role of Cellular Senescence in Carpal Tunnel Syndrome - Project Summary/Abstract Carpal Tunnel Syndrome (CTS) is an idiopathic, non-inflammatory, age-related fibrotic disorder resulting in compression of the median nerve that affects 10 million Americans annually. Despite the prevalence, cost, and societal impact of CTS, little progress in its treatment and prevention has been made in the past 50 years, primarily due to the lack of mechanistic understanding of disease etiology. Aging is a major risk factor not only for CTS, but also for fibrosis and cellular senescence. Senescent cells exhibit a senescence-associated secretory phenotype (SASP) that is important for wound healing; however, failure to limit this response appropriately leads to fibrotic disease phenotypes. Our preliminary data shows that markers of cellular senescence, including senescence associated β-galactosidase, p16Ink4a, p53; immune evasion markers, as well as SASP factors are increased in both the tissue and cells of the subsynovial connective tissue (SSCT) of CTS patients. Further we have found that type II interferon ɣ (IFNɣ) is expressed in the SASP, and that it induces immune evasion markers. Moreover, targeting senescent pathways in human SSCT cultures using the senolytics dasatinib + quercetin reduces markers of senescence and fibrosis. Thus, our central hypothesis is that senescent cell accumulation in the SSCT is causally implicated in pathological aging and fibrosis found in CTS and that elimination of these senescent cells in the SSCT will attenuate the progression of this pathological fibrosis and thus alleviate disease progression. Importantly, we have developed a rabbit model of CTS and progressive SSCT fibrosis that will allow us to study disease mechanisms in vivo. Therefore, to test this hypothesis, we propose the following specific aims: 1) elucidate the mechanism by which IFNɣ promotes senescence and immune evasion in the SSCT, 2) determine the contribution of senescence to fibrosis in CTS, and 3) evaluate senolytic therapy in vivo. This work will significantly and fundamentally advance our understanding of SSCT fibrosis in CTS, which is a disease of aging and is associated with multiple age-related metabolic co-morbidities. Our discovery of increased senescent fibroblast expression of type IFNɣ in fibrotic tissue and cells could provide a novel therapeutic target for resolution of tissue fibrosis. The innovative aspects of this project are: it will critically test the heretofore untested hypothesis that senescent cells promote CTS, address fundamental questions about disease-related senescent cells, test the novel hypothesis that targeting senescence cells will be a novel therapeutic strategy for CTS and for the first time explore the role of IFNɣ on CTS pathology. This work aligns well with the “Geroscience Hypothesis” which postulates that interventions that slow the aging process will simultaneously delay the appearance or severity of many chronic age-related diseases. CTS is associated with multiple co-morbidities and thus, in addition to advancing the field of aging and fibrosis biology, novel targeted strategies for CTS treatment and prevention derived from these studies could rapidly be translated into new, non-surgical therapies for the millions of people who suffer with CTS.


Issue Date FY	Funding FY	Legal Entity Name	Legal Entity Address	Legal Entity City	Legal Entity State	Legal Entity Zip Code	Legal Entity COUNTY	Legal Entity COUNTRY	Assistance Listing	Award Code	Budget Year	Action Date	Action Type	Action Amount

Issue Date FY: 2026 ( Subtotal = $603,632 )
2026	2026	MAYO CLINIC	200 1ST ST SW	ROCHESTER	MN	55905	OLMSTED	USA	Arthritis, Musculoskeletal and Skin Diseases Research	000	6	12/5/2025	NON-COMPETING CONTINUATION	$603,632
														Subtotal = $603,632

Issue Date FY: 2025 ( Subtotal = $650,582 )
2025	2025	MAYO CLINIC	200 1ST ST SW	ROCHESTER	MN	55905	OLMSTED	USA	Arthritis, Musculoskeletal and Skin Diseases Research	001	5	6/4/2025	NON-COMPETING CONTINUATION	$46,950
2025	2025	MAYO CLINIC	200 1ST ST SW	ROCHESTER	MN	55905	OLMSTED	USA	Arthritis, Musculoskeletal and Skin Diseases Research	000	5	11/27/2024	NON-COMPETING CONTINUATION	$603,632
														Subtotal = $650,582

Issue Date FY: 2024 ( Subtotal = $650,582 )
2024	2024	MAYO CLINIC	200 1ST ST SW	ROCHESTER	MN	55905	OLMSTED	USA	Arthritis, Musculoskeletal and Skin Diseases Research	000	4	12/7/2023	NON-COMPETING CONTINUATION	$603,632
2024	2024	MAYO CLINIC	200 1ST ST SW	ROCHESTER	MN	55905	OLMSTED	USA	Arthritis, Musculoskeletal and Skin Diseases Research	001	4	6/18/2024	NON-COMPETING CONTINUATION	$46,950
														Subtotal = $650,582

Issue Date FY: 2023 ( Subtotal = $670,703 )
2023	2023	MAYO CLINIC	200 FIRST ST SW	ROCHESTER	MN	55905	OLMSTED	USA	Arthritis, Musculoskeletal and Skin Diseases Research	001	3	2/27/2023	NON-COMPETING CONTINUATION	$67,071
2023	2023	MAYO CLINIC	200 FIRST ST SW	ROCHESTER	MN	55905	OLMSTED	USA	Arthritis, Musculoskeletal and Skin Diseases Research	000	3	12/16/2022	NON-COMPETING CONTINUATION	$603,632
2023	2020	TRUSTEES OF INDIANA UNIVERSITY	980 INDIANA AVE RM 2232	INDIANAPOLIS	IN	46202	MARION	USA	Arthritis, Musculoskeletal and Skin Diseases Research	002	1	5/8/2023	NEW	-$1,056
2023	2020	MAYO CLINIC	200 1ST ST SW	ROCHESTER	MN	55905	OLMSTED	USA	Arthritis, Musculoskeletal and Skin Diseases Research	003	2	5/8/2023	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$1,056
														Subtotal = $670,703

Issue Date FY: 2022 ( Subtotal = $1,460 )
2022	2020	MAYO CLINIC	200 FIRST ST SW	ROCHESTER	MN	55905	OLMSTED	USA	Arthritis, Musculoskeletal and Skin Diseases Research	001	2	9/21/2022	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$464,293
2022	2020	TRUSTEES OF INDIANA UNIVERSITY	980 INDIANA AVE RM 2232	INDIANAPOLIS	IN	46202	MARION	USA	Arthritis, Musculoskeletal and Skin Diseases Research	000	1	9/21/2022	NEW	-$462,833
														Subtotal = $1,460

Issue Date FY: 2021 ( Subtotal = $0 )
2021	2020	TRUSTEES OF INDIANA UNIVERSITY	980 INDIANA AVE RM 2232	INDIANAPOLIS	IN	46202	MARION	USA	Arthritis, Musculoskeletal and Skin Diseases Research	001	1	9/2/2021	NEW	$0
2021	2020	TRUSTEES OF INDIANA UNIVERSITY	980 INDIANA AVE RM 2232	INDIANAPOLIS	IN	46202	MARION	USA	Arthritis, Musculoskeletal and Skin Diseases Research	000	1	3/16/2021	NEW	$0
														Subtotal = $0

Issue Date FY: 2020 ( Subtotal = $667,759 )
2020	2020	TRUSTEES OF INDIANA UNIVERSITY	980 INDIANA AVE RM 2232	INDIANAPOLIS	IN	46202	MARION	USA	Arthritis, Musculoskeletal and Skin Diseases Research	000	1	9/10/2020	NEW	$667,759
														Subtotal = $667,759

Grand Total All Awards = $3,244,718

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The Role of Cellular Senescence in Carpal Tunnel Syndrome

Award Number: R01AR076347

ORGANIZATION: NATIONAL INSTITUTE OF ARTHRITIS & MUSCULOSKELETAL & SKIN DISEASES

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

PERIOD OF PERFORMANCE START DATE: 09/10/2020

PERIOD OF PERFORMANCE END DATE: 11/30/2026

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